The proposed work is directed toward the elucidation of various factors which control or modulate insulin secretion under physiological conditions. For example, we will investigate the effects of divalent cations such as magnesium and calcium on insulin release, as well as hypothalamic factors such as somatostatin. We will also study the role of the central nervous system on influencing insulin output. This will be accomplished by utilizing a vascularly isolated, but normally innervated, in situ perfused pancreas preparation with the cephalad portion of the animal, including the brain, intact. Thus we can stimulate precise brain centers (e.g., hypothalamic nuclei) under stereotaxic control, and demonstrate whether or not there exists a direct CNS pathway to the pancreas which is of physiological importance. We will also be able to ascertain the effect of insulin, glucose, amines, etc. on insulin output when infused only into the cephalad vasculature. We will also investigate the action of the liver on modifying peripheral insulin levels by observing endogenous insulin uptake/degradation by the liver during one flow cycle through a viable liver-pancreas preparation which has been subjected to a constant glucose infusion. BIBLIOGRAPHIC REFERENCES: Curry, D. L., C. H. Li and L. L. Bennett. Dynamics of Insulin Secretion by Perfused Hamster Pancreases... Effects of Hypophysectomy, Bovine and Human Growth Hormone and Prolactin. J. Endocrinology 65: 245-251, 1975. Curry, D. L. and L. L. Bennett. Does Somatostatin Inhibition of Insulin Secretion Involve Two Mechanisms of Action? National Academy of Sciences Proceedings 73: 248-251, 1976.